tbuckley/cabot-search huggingface dataset:
An audit of neoadjuvant chemotherapy in sinonasal teratocarcinosarcoma from an academic tertiary care centre in India.
Authors: Zoya Ravish Peelay, Vijay Maruti Patil, Vanita Noronha, Ajaykumar Chandrabhan Singh, Kumar Prabhash, Minit Jalan Shah, Nandini Sharrel Menon
Journal: Journal of Clinical Oncology (2023)

e18109 Background: Sinonasal teratocarcinosarcoma (SNTCS) are rare types of sinonasal malignancies, incidence is approximately 3% of all head and neck cancers and less than 1% of all tumors. There is very limited literature available on SNTCS and most of the literature available is in the form of case reports and small case series. The management of these tumors is complicated because of the location and paucity of data available in such scenarios where resection becomes difficult in extensive disease and the role of neoadjuvant chemotherapy (NACT) becomes significant. This audit was performed to study the tolerance and outcomes with NACT followed by surgery(Sx) in these treatment protocols. Methods: A retrospective analysis of a prospectively maintained database approved by the IEC of TMH. The baseline characteristics, extent of tumor, type of NACT, adverse events was curated from the EMR and patients' hospital files. Patients with clinically or radiologically extensive/inoperable disease at presentation were planned for NACT for a duration of 6-8 weeks. Post NACT these patients underwent axial imaging for response assessment.(RECIST v1.1). The adverse events due to NACT were noted as per CTCAE v5.0. Results: There were 27 patients of SNTCS. The median age of the whole cohort was 42 years (IQR 30-56) and 85.2% (n=23) were male. The ECOG PS was 0-1 in 24 (88.8%) patients and only 3 (11.1%) patients had ECOG PS 2. 17 patients (63%) had a history of addiction. 7 patients had clinical palpable regional nodes (25.9%) and 1 patient (3.7%) had lung metastasis at presentation. All 27 patients received NACT in view of extensive disease .15 patients (55.6%) had intracranial extension of disease with intradural extension. Only 10 patients (37%) had intraparenchymal disease. 22 patients (81.5%) had Kadish stage C-D disease and the remaining 5 patients (18.5%) had Kadish stage B at baseline. 20 patients (74.1%) received Cisplatin &amp; Etoposide as NACT and remaining 7 received other chemotherapy. Median number of chemotherapy cycles was 2 (Q1 is 2 - Q3 is 3). 1 patient (3.7%) did not complete the planned NACT due to toxicity. The incidence of grade 3-5 toxicity in accordance with CTCAE version 5.0 was 37.03%. There was 1 death (3.7%) due to chemotherapy toxicity. Details of response to NACT are given in the table. 18 patients (77.8%) underwent Sx, 5 patients (18.5%) received CTRT and 2 patients (7.4%) received definitive RT and 2 patients (7.4%) did not receive any local therapy .Post Sx in local node was found in 3 patients (11.11%).The 2 years progression free survival was 53.2%(95%CI 31.3 - 70.9) and 2 years overall survival was 60.9%(95%CI 37.6 - 77.8). Conclusions: NACT improves survival in locally advanced SNTC with significant response rates. [Table: see text]
Patients characteristics, treatment patterns and clinical outcomes in patients with head and neck squamous cell carcinoma (aHNSCC) receiving immunotherapy in advanced setting: Retrospective cohort analysis of real-world data in Spain.
Authors: Ana Laura Ortega Granados, German Paolo Vinueza, Jose Antonio Lopez Lopez, Francisco José García Verdejo, Fernando Gálvez Montosa, Natalia Luque Caro, María Ruiz Sanjuan, Leticia Diaz Beltran, Capilla de la Torre Cabrera, Mónica Fernández Navarro, Nuria Cárdenas Quesada, Miguel Angel Moreno Jimenez, Juan Francisco Marin Pozo, Pedro Sanchez Rovira
Journal: Journal of Clinical Oncology (2023)

e18033 Background: This retrospective cohort analysis looked at real-world data from Spain to better understand the characteristics, treatment patterns and clinical outcomes of patients with aHNSCC who received immunotherapy in an advanced setting. In aHNSCC, the standard of care was platinum-based chemotherapy. However, this treatment modality is associated with significant toxicity and only a minority of patients achieve long-term disease control. As a result, there was an unmet need for effective and well-tolerated treatment till immunotherapy has shown efficacy in some clinical trials. However, data on the use of immunotherapy in routine clinical practice are limited. The aim of this study was to characterize the real-world safety and effectiveness of immunotherapy in patients with aHNSCC in real practice. Methods: This was a retrospective cohort study that included data from our database, a tertiary hospital in Spain. Patients with a diagnosis of aHNSCC who received immunotherapy between 2017 and 2022 were included, excluding those in clinical trials. Clinical outcomes assessed were overall survival (OS), progression-free survival (PFS), response rate (RR), and toxicity profile. 97 patients were included in the analysis. The most common histological subtype was oral cavity cancer (43%), followed by laryngeal cancer (29%). Results: The majority of patients had stage IVA-B disease at diagnosis (62%). A 53% of patients received first line nivolumab as monotherapy, or pembrolizumab as monotherapy or combined with platinum chemotherapy, and a 58% of patients received second or third line nivolumab as monotherapy.With a median age of 64 years (range: 45-86), most patients received it as second-line or later treatment (70%). The overall response rate was 29%, with durable responses seen in some patients (28% longer than 1 y). The median overall survival was 13.9 months in first-line setting (3-24 mo), and the 1-year survival rate was 36%. In second-line setting, the median OS was 11.1 mo (3-89 mo), and 1-year survival rate was 33%. More frequent toxicities were skin (26%) and endocrine (21%). We had 8 cases of hyperprogressive disease (8.2%) and treatment was interrupted due toxicity in 6 patients. Conclusions: These results are very close to results found in clinical trials (KEYNOTE-048, CheckMate 141) and confirm that immunotherapy is safe and impacts on survival of aHNSCC patients. We need to identify predictive biomarkers for response and toxicity.
The efficacy of radical hepatectomy versus stereotactic body radiotherapy for primary hepatocellular carcinoma: A propensity score matching analysis.
Authors: Yulin Hu, Feng-Ming Spring Kong, Ren Ji
Journal: Journal of Clinical Oncology (2023)

4130 Background: Recent international guidelines have included stereotactic body radiotherapy (SBRT) which outstanding tumor control as a treatment option for hepatocellular carcinoma (HCC) in several settings. However, data evaluating surgery and SBRT are limited, and results published were controversial. The retrospective study aims to compare the efficacy of hepatectomy and SBRT for HCC. Methods: The study population started with patients in databases of primary HCC, treated with curative hepatectomy or SBRT, regardless of tumor number, tumor size, cirrhosis and portal vein thrombosis. Patients with prior cancer treatment other than transarterial chemoembolization were excluded. In order to reduce the potential confounding effect of treatment and selection bias, 3-to-1 propensity score models were constructed based on each patient’s estimated propensity score. The variables significant for overall survival were considered for the match, including age, sex, Child-Pugh score, ECOG performance status score, maximum diameter, BCLC stage, prothrombin time, total bilirubin, albumin, and white blood cell. Overall survival and progression-free survival were compared. Results: A total of 174 patients, 154 in hepatectomy group and 20 in SBRT group, were analyzed. 125 men and 29 women, mean 56.2 years of age, in hepatectomy group. 12 men and 8 women, mean 70.5 years of age, in SBRT group. ECOG was a significant favorable factor for overall survival. Maximum diameter, portal vein embolization, aspartate transferase and albumin was significant favorable factors for disease-free survival of patients with primary hepatocellular carcinomas. Before PSM, patients in the hepatectomy group tended to be younger, had better performance status, less cirrhosis, less tumor number and had better hepatic function than those in the SBRT group ( P &lt; .05). The 3-year overall survival rate and median progression-free survival time for the surgical resection and SBRT groups were 77.9% vs 35.4 (P = .003) and 30 vs 20 month (P = .486), respectively. After PSM, 80 patients, 60 in hepatectomy group and 20 in SBRT group, were analyzed. The 3-year overall survival rate and median progression-free survival time for the surgical resection and SBRT groups were 71.9% vs 56.6 (P = .92) and 17 vs 26 month (P = .656), respectively. The patients of hepatectomy group had less cirrhosis, better liver function and less tumor number than those in 20 with SBRT. Conclusions: For primary HCC, regardless of tumor size and tumor number, stereotactic body radiotherapy can provide similar result on overall survival and tumor control compared to hepatectomy. Stereotactic body radiotherapy can also be less invasive and provide less inpatient time. So stereotactic body radiotherapy can be a effective treatment for patients with primary HCC.
Independent biomarkers predictive of outcomes with enfortumab vedotin (EV) in patients (pts) with advanced urothelial carcinoma (aUC): Analysis of the UNITE study.
Authors: Tanya Jindal, Li Zhang, Cindy Jiang, Deepak Kilari, Omar Alhalabi, Amanda Nizam, Arnab Basu, Mehmet Asim Bilen, Yousef Zakharia, Matthew I. Milowsky, Sumit Shah, Christopher J. Hoimes, Nancy B. Davis, Shilpa Gupta, Hamid Emamekhoo, Petros Grivas, Joaquim Bellmunt, Matthew T Campbell, Ajjai Shivaram Alva, Vadim S Koshkin
Journal: Journal of Clinical Oncology (2023)

4573 Background: EV is used for treatment-refractory aUC with activity also noted in a frontline trial. Independent biomarkers associated with EV treatment outcomes are lacking. Methods: UNITE is a multi-site retrospective study of pts treated with EV and other agents. In this analysis we included pts treated with EV monotherapy and available next generation sequencing (NGS) data. Assessed biomarkers included genomic alterations (alts) in ≥5% of pts, tumor mutation burden (TMB) and PD-L1 expression. Pts were evaluable for observed response rate (ORR) if they had scans after ≥1 EV cycle. Biomarkers were evaluated individually in univariate analyses (UVA) and in separate multivariate analyses (MVA) which accounted for clinical variables. Progression-free survival (PFS) and overall survival (OS) from EV start were assessed using Kaplan Meier method and cox proportional hazard (cph) modeling. ORR was assessed using logistic regression. Results: Among 303 pts with NGS treated with EV monotherapy at 16 US sites, 207 had TMB and 146 had PD-L1 data. Median age was 70; 218 (72%) men, 262 (87%) White, 196 (66%) with pure urothelial histology, 212 (71%) with lower tract primary tumor, 204 (67%) had ≥2 prior therapies. ORR was 53% (140/264); mPFS was 6.0 mos, mOS was 13.1 mos. In UVA, longer OS was associated with higher Hgb, albumin and GFR (&gt;30cc/min), lower neutrophil to lymphocyte ratio, older age, and absence of liver mets. MVA included these variables along with histology as covariates. In multivariate cph models, better outcomes were associated with alts in ERBB2, KDM6A and PIK3CA, while inferior outcomes with low TMB (&lt;10 Mut/Mb) and high PD-L1 (CPS ≥ 10). Conclusions: MVA of this large, multi-site, retrospective cohort of aUC pts, identified several putative biomarkers independently associated with EV treatment outcomes. Longer OS was associated with ERBB2 and KDM6A alts, low PD-L1 and high TMB. Limitations include lack of central scan review, pt selection and confounding biases. These findings require external validation, while their underlying mechanisms merit translational study. [Table: see text]
Safety and efficacy of trifluridine/tipiracil plus bevacizumab in RAS mutated patients with metastatic colorectal cancer.
Authors: Vasiliki Michalaki, Thedosios Theodosopoulos, Antonios Vezakis, Ioannis Papaconstantinou, Ioannis Kontis, Nikolaos Dafnios, George Frangoulidis, Despina Karandrea, Christos Papadimitriou
Journal: Journal of Clinical Oncology (2023)

e15605 Background: Trifluridine-tipiracil (FTD/TPI) plus bevacizumab has shown efficacy inrefractory metastatic colorectal cancer (mCRC); however, evidence supporting the role of this combination in Ras mutated population, is limited. In this phase II study, we investigated the efficacy and safety profiles of FTD/TPI in mCRC according to KRAS status. Methods: Eligible patients were mCRC refractory or intolerant to all standard therapies including fluoropyrimidines, irinotecan and oxaliplatin. Patients received 4-week cycles of treatment with FTD/TPI (35 mg/m 2 , twice daily, days 1-5 and 8-12) and bevacizumab (5 mg/kg, days 1 and 15). Clinicopathological characteristics, overall response rate (ORR), disease control rate (DCR), PFS, and safety data were collected and analyzed. Results: Forty-two patients were enrolled. Median age was 67 years (range 41–79 years), 44% were male, 100% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1, 85% were KRAS and 15% NRAS mutant, and 75% underwent primary tumor resection; 68% of patients had liver metastases, 49% had lung metastases, and 18% had peritoneal carcinomatosis. The median number of previous treatment lines was 2 (range1–3), and 85% of patients received at least one previous anti-angiogenic agent. DCR was 57.1% (90% CI, 44.6 %-69.3%, P = 0.0690), respectively. The median progression-free survival (PFS) was 4.6 months. The most common grade 3 or higher adverse event was neutropenia (54%), and anemia (16%); 32% of patients required either dose delays or dose reductions due to toxicity. No treatment-related deaths occurred. Conclusions: FTD/TPI is an important therapeutic resource in refractory RAS mutated metastatic colorectal cancer that combines manageability and safety.
Optical genome mapping for cytogenomic analysis of hematological neoplasms.
Authors: Guilin Tang, Zhenya Tang, Rashmi Kanagal-Shamanna, Hagop M. Kantarjian, Guillermo Garcia-Manero, Branko Cuglievan, David McCall, Preetesh Jain, Melissa Robinson, Alex Reynolds, Christopher P Danos, Griselda Jazmin Cardona, Christopher P Geiger, Su Yang, L Jeffrey Medeiros, Gokce A Toruner
Journal: Journal of Clinical Oncology (2023)

e19016 Background: Optical genome mapping (OGM) provides a genome-wide analysis for structural variants and copy number changes in one-assay. Compared with conventional G-banded karyotyping (GBK), OGM provides significantly higher resolution and does not require metaphase cells. In this study, we assessed the added value of OGM for cytogenomic analysis of hematological neoplasms. Methods: OGM was performed on blood or bone marrow using Saphyr from Bionano Genomics on 63 patients diagnosed with various types of hematological malignancy (see Table). Variant calling was made by the Rare Variant Analysis pipeline on Bionano Access after applying recommended filters. Each patient had karyotype and/or fluorescence in situ hybridization (FISH) results available for comparison and confirmation. Only Tier 1 (pathogenic) and Tier 2 (likely pathologic) abnormalities were included for comparison purposes in this study. Results: The results were completely concordant between GBK/FISH and OGM in 30 (47.6%) patients, including 10 patients who showed no cytogenetic abnormality (normal). Fully discordant results were found in 8 (12.7%) patients: 2 had an abnormal karyotype but normal OGM, the discrepancy was mainly due to the clonal size (&lt;20%) below the limitation of detection of OGM; 6 had a normal karyotype but cytogenetic abnormalities were detected by OGM, the discrepancy was mainly due to failure of tumor cells growth (n=5) or subtle cytogenetic abnormality undetectable by GBK (n=1). Partially concordant results between karyotype/FISH and OGM were observed in 25 (40%) patients, some abnormalities were detected by both, some were detected by GBK alone (n=4) or by OGM alone (n=25), the latter group included 10 cases with chromothripsis which only be detected by OGM. Overall, OGM provided clinically significant information in 14 (22%) patients regarding diagnosis, risk stratification, and/or identifying therapeutic targets. The added value was more common in lymphoid neoplasms (9 of 27 patients, 33%). Conclusions: OGM provides additional clinically relevant cytogenetic information in the workup of hematological neoplasms. This added value is more apparent in lymphoid neoplasms. These improvements are largely contributable to the higher resolution provided by OGM and analysis independent of metaphase cells. A major limitation of OGM usage is the need for a clonal size of at least 20%. [Table: see text]
A characteristic comparison of cell-free DNA isolated from plasma and cerebrospinal fluid in patients with cancer.
Authors: Jian Zhang, Wei Wang, Yingmei Li
Journal: Journal of Clinical Oncology (2023)

e14008 Background: Cell-free DNA (cfDNA) from plasma has proved its power as a liquid biopsy analyte in many cancer types, except cancers from central nervous system (CNS). CfDNA from cerebrospinal fluid (CSF) better recapitulates mutations for primary CNS tumors or cancer brain metastasis. The characteristics of cfDNA from plasma, including concentration range, mutation frequency, length, end motif etc. have been thoroughly studied, while the features of cfDNA from CSF are yet to be investigated. Methods: We retrospectively reviewed records since 2021 from a clinical sequencing center, and selected samples from patients with non-small cell lung cancer. CfDNA from 30 CSF and 85 plasma samples was isolated, followed by NGS library preparation procedures, and enriched with a 680-gene panel. Fragmentation features including cfDNA length distribution and frequency of 6-bp end motif sequences were analyzed after removal of UMI. K-means clustering algorithm was utilized to analyze fragment motifs. Results: The mean concentration of cfDNA isolated from plasma and CSF was 13.46 ng/mL (1.28 – 96.40, 95%) and 26.82 ng/mL (2.80-382.00, 95%) respectively. A larger proportion of longer cfDNA fragments (&gt;200bp) in CSF sample was observed, 37.8% in CSF VS 22.8% in plasma. Several end motifs were identified to be highly enriched in either sample type, and we found that sample types could be separated by K-means clustering from top 10 motifs. Conclusions: CSF is a less complicated solution system than plasma, regarding chemical constitutes. The cfDNA length distribution and motif patters are distinguishable in CSF and plasma. Our analysis demonstrated that the characteristics of cfDNA in CSF are obviously different from cfDNA in plasma, and the underlying mechanism remains to be clarified.
First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) in patients (pts) with microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): 64-month (mo) follow-up from CheckMate 142.
Authors: Heinz-Josef Lenz, Michael J. Overman, Eric Van Cutsem, M. Luisa Limon, Mark Ka Wong, Alain Hendlisz, Massimo Aglietta, Pilar Garcia-Alfonso, Bart Neyns, Fabio Gelsomino, Dana Backlund Cardin, Tomislav Dragovich, Usman Shah, Stephen M. McCraith, Abigail Wang, Ming Lei, Jin Yao, Lixian Jin, Sara Lonardi
Journal: Journal of Clinical Oncology (2023)

3550 Background: NIVO + IPI demonstrated robust, durable clinical benefit, and was well tolerated as a 1L therapy in pts with MSI-H/dMMR mCRC in the phase 2 CheckMate 142 study (NCT02060188), leading to the inclusion of NIVO + IPI in the NCCN guidelines as an initial therapy option for these pts. At 52-mo median follow-up, 1L NIVO + IPI continued to demonstrate durable clinical benefit, and no new safety signals were identified. Here we report longer follow-up results. Methods: Pts with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by investigator assessment (INV) per RECIST v1.1. Other key endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), all by INV; overall survival (OS); and safety. Results: In total, 45 pts received 1L NIVO + IPI. With median follow-up of 64.2 mo (range, 59.4–68.9 mo), ORR by INV was 71% (95% CI, 56–84%). The proportion of pts with a best overall response of complete response (CR) was 20%, partial response (PR) was 51%, stable disease (SD) was 13%, and progressive disease was 16%. Median DOR (mDOR) was not reached, and the 60-mo DOR rate was 72%. Median PFS (mPFS) by INV and median OS (mOS) were not reached, with 60-mo PFS and OS rates of 55% and 67%, respectively (Table). Among pts alive at the data cutoff (n = 31), 30 remained treatment-free after initial study treatment without receiving any subsequent systemic therapy, with a median treatment-free interval of 34.7 mo (range, 1.6–61.4 mo). Exploratory analysis by tumor mutational burden status will be presented. Safety data are shown in the Table. Conclusions: At 64-mo follow-up, NIVO + IPI continued to demonstrate clinically meaningful survival and durable responses, with mPFS, mOS, and mDOR still not reached, suggesting the potential for long-term clinical benefit. Safety remained consistent with previous data. These findings further support current recommendations for NIVO + IPI as a 1L treatment for pts with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188 . [Table: see text]